癫痫发作和癫痫新药进展报告:第 17 届埃拉特抗癫痫新药与新设备会议(EILAT XVII)摘要。II.处于临床开发后期的药物。

IF 6.6 1区 医学 Q1 CLINICAL NEUROLOGY Epilepsia Pub Date : 2024-08-22 DOI:10.1111/epi.18075
Meir Bialer, Svein I. Johannessen, Matthias J. Koepp, Emilio Perucca, Piero Perucca, Torbjörn Tomson, H. Steve White
{"title":"癫痫发作和癫痫新药进展报告:第 17 届埃拉特抗癫痫新药与新设备会议(EILAT XVII)摘要。II.处于临床开发后期的药物。","authors":"Meir Bialer,&nbsp;Svein I. Johannessen,&nbsp;Matthias J. Koepp,&nbsp;Emilio Perucca,&nbsp;Piero Perucca,&nbsp;Torbjörn Tomson,&nbsp;H. Steve White","doi":"10.1111/epi.18075","DOIUrl":null,"url":null,"abstract":"<p>The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy-related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, K<sub>V</sub>7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT<sub>2C</sub> receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the <i>GRIN1</i>, <i>−2A</i>, <i>-2B</i>, or <i>-2D</i> genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Na<sub>v</sub>1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.</p>","PeriodicalId":11768,"journal":{"name":"Epilepsia","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18075","citationCount":"0","resultStr":"{\"title\":\"Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development\",\"authors\":\"Meir Bialer,&nbsp;Svein I. Johannessen,&nbsp;Matthias J. Koepp,&nbsp;Emilio Perucca,&nbsp;Piero Perucca,&nbsp;Torbjörn Tomson,&nbsp;H. Steve White\",\"doi\":\"10.1111/epi.18075\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy-related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, K<sub>V</sub>7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT<sub>2C</sub> receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the <i>GRIN1</i>, <i>−2A</i>, <i>-2B</i>, or <i>-2D</i> genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Na<sub>v</sub>1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.</p>\",\"PeriodicalId\":11768,\"journal\":{\"name\":\"Epilepsia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2024-08-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/epi.18075\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epilepsia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/epi.18075\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epilepsia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/epi.18075","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

摘要

第 17 届埃拉特抗癫痫新药与新设备会议于 2024 年 5 月 5-8 日在西班牙马德里举行。与往常一样,本次会议的核心内容是介绍处于不同开发阶段的癫痫相关适应症的研究药物。有关处于临床前或早期临床开发阶段的化合物的信息摘要载于随附出版物(第一部分)。在这篇文章中,我们提供了五种处于临床开发后期的化合物的摘要,即已获得一些有关癫痫患者抗癫痫活性信息的化合物。这些研究治疗药物包括 azetukalner (XEN1101),这是一种强效、KV7.2/7.3特异性钾通道开启剂,正在开发用于治疗局灶性癫痫发作、全身强直阵挛发作和重度抑郁症;bexicaserin (LP352),一种选择性 5-HT2C 受体超拮抗剂,正在开发用于治疗与发育性和癫痫性脑病相关的癫痫发作;radiprodil,一种含 NR2B 亚基的 N-甲基-D-天冬氨酸谷氨酸受体的选择性负异位调节剂,正在开发中,用于治疗与 GRIN1、-2A、-2B 或 -2D 基因功能增益突变所致疾病相关的癫痫发作和行为表现;soticlestat (TAK-935),一种胆固醇 24- 羟化酶选择性抑制剂,正在开发中,用于治疗与德雷维综合征和伦诺克斯-加斯托综合征相关的癫痫发作;以及 STK-001,一种反义寡核苷酸,旨在上调 Nav1.1蛋白的表达并改善德雷维综合征患者的预后。这些药物的作用机制各不相同,说明了在发现癫痫发作和癫痫的新疗法时所采用的不同方法。本报告中讨论的两种化合物(azetukalner 和 soticlestat)已经在随机安慰剂对照辅助治疗试验中获得了临床疗效证据。至于其他化合物,迄今尚未完成充分有效的安慰剂对照疗效试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Progress report on new medications for seizures and epilepsy: A summary of the 17th Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVII). II. Drugs in more advanced clinical development

The 17th Eilat Conference on New Antiepileptic Drugs and Devices took place in Madrid, Spain on May 5–8, 2024. As usual, the core part of the conference consisted of presentations on investigational drugs at various stages of development for epilepsy-related indications. Summaries of information on compounds in preclinical or early clinical development are included in an accompanying publication (Part I). In this article, we provide summaries for five compounds in more advanced clinical development, i.e. compounds for which some information on antiseizure activity in individuals with epilepsy is available. These investigational treatments include azetukalner (XEN1101), a potent, KV7.2/7.3-specific potassium channel opener in development for the treatment of focal seizures, generalized tonic–clonic seizures, and major depressive disorder; bexicaserin (LP352), a selective 5-HT2C receptor superagonist in development for the treatment of seizures associated with developmental and epileptic encephalopathies; radiprodil, a selective negative allosteric modulator of NR2B subunit-containing N-methyl-D-aspartate glutamate receptors, in development for the treatment of seizures and behavior manifestations associated with disorders caused by gain-of-function mutations in the GRIN1, −2A, -2B, or -2D genes; soticlestat (TAK-935), a selective inhibitor of cholesterol 24-hydroxylase in development for the treatment of seizures associated with Dravet syndrome and Lennox–Gastaut syndrome; and STK-001, an antisense oligonucleotide designed to upregulate Nav1.1 protein expression and improve outcomes in individuals with Dravet syndrome. The diversity in mechanisms of action of these agents illustrates different approaches being pursued in the discovery of novel treatments for seizures and epilepsy. For two of the compounds discussed in this report (azetukalner and soticlestat), clinical evidence of efficacy has already been obtained in a randomized placebo-controlled adjunctive-therapy trial. For the other compounds, adequately powered placebo-controlled efficacy trials have not been completed to date.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Epilepsia
Epilepsia 医学-临床神经学
CiteScore
10.90
自引率
10.70%
发文量
319
审稿时长
2-4 weeks
期刊介绍: Epilepsia is the leading, authoritative source for innovative clinical and basic science research for all aspects of epilepsy and seizures. In addition, Epilepsia publishes critical reviews, opinion pieces, and guidelines that foster understanding and aim to improve the diagnosis and treatment of people with seizures and epilepsy.
期刊最新文献
Histopathological substrate of increased T2 signal in the anterior temporal lobe white matter in temporal lobe epilepsy associated with hippocampal sclerosis. Imaging blood-brain barrier dysfunction in drug-resistant epilepsy: A multi-center feasibility study. Long-term neuroplasticity in language networks after anterior temporal lobe resection. Eating habits and behaviors in children with Dravet syndrome: A case-control study. Machine learning for forecasting initial seizure onset in neonatal hypoxic-ischemic encephalopathy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1